1. Field of the Invention
This invention relates to 3-acetyl-1-aryl-pyrazole derivatives useful in the control of insects, nematodes or helminths, and to compositions containing the same. The method of the invention particularly relates to the application of the 1-arylpyrazole derivatives under conditions where some worker exposure is likely to occur. The invention also relates to a new and improved method of control of insects, nematodes or helminths, using an insecticidally active material having a 1-phenyl pyrazole group therein and is particularly useful for the control of aphids.
2. Description of the Related Art
The control of insects, nematodes or helminths by means of active material having a 1-arylpyrazole group therein has been described by many patents or patent applications such as International Patent Publication No. WO 93/06089 (and the equivalent U.S. Pat. No. 5,451,598), WO 94/21606 and WO 87/03781 as well as in European Patent Publication Numbers 0295117, 659745, 679650, 201852 and 412849, German Patent No. DE19511269 and U.S. Pat. No. 5,232,940.
The first object of the instant invention is to provide an improved level of safety to the user and the environment in the methods of control of insects, nematodes or helminths. All pesticides are generally more or less hazardous, and it is always desirable to lower the potential hazards which might exist even if these are quite low and acceptable for normal uses. Thus it is an object of the instant invention to develop a method of control wherein the potential hazards are lowered by comparison with the known and existing methods, even if these existing hazards are low and acceptable.
A second object of the invention is to lower the hazards for working people in such methods of use. A third object of the present invention is to lower the hazards for working people in such methods of use when a substantial exposure might occur.
A fourth object of the present invention is to provide a new and better method of control of aphids. The control of aphids by many insecticidally active materials is known but these insect species are capable of extremely rapid population growth with a substantial and higher risk of resistance developing to pesticides than occurs for other insect species. Thus it is highly desirable to be able to introduce new methods of control using pesticides other than those used up to now. It is an object of the instant invention to provide a method of control using insecticidally active material of the 1-phenyl pyrazole type which has a high efficiency, and if possible, a better efficiency than the methods known up to now.
A fifth object of the present invention is to provide new 1-phenylpyrazole derivatives which possess improved systemic aphicidal activity compared to known compounds. These compounds possess excellent properties in controlling cotton leaf aphid (Aphis gossypii) and greenbug (Schizaphis graminum) in systemic applications.
These and other objects of the invention shall become readily apparent from the description of the present invention which follows, and are achieved in whole or in part by the invention.
This invention provides an improvement in a method of control of insects by means of application of an insecticidally active ingredient having a 1-arylpyrazole group to a locus where insects are present or expected to be present, said application being made under conditions whereby an exposure of mammalian species, especially a substantial exposure, may occur, the improvement whereby the said active ingredient has a 3-acetyl substituent on the pyrazole ring. The method of control of the invention is particularly suitable when there may be an exposure to working people.
The invention also provides a method of control of insects by means of application of an insecticidally active ingredient having a 1-arylpyrazole group to a locus where aphids insects are present or expected to be present, the improvement whereby the said active ingredient has a 3-acetyl substituent on the pyrazole ring.
Practically the applications according to the inventions are using an active ingredient of formula (I): 
wherein:
R1 is S(O)mR5;
R2 is selected from a hydrogen atom, a halogen atom xe2x80x94NR6R7, xe2x80x94S(O)nR8, C(O)R8, C(O)OR9, alkyl, haloalkyl, xe2x80x94OR9, or xe2x80x94Nxe2x95x90C(R10)(R11);
R3 is selected from a halogen atom or the hydrogen atom;
R4 is selected from a halogen atom, haloalkyl, haloalkoxy, xe2x80x94S(O)pCF3, or xe2x80x94SF5;
R5 is alkyl or haloalkyl;
R6 and R7 are independently selected from a hydrogen atom, alkyl, haloalkyl, xe2x80x94C(O) R8, C(O)OR8, xe2x80x94S(O)qCF3; the alkyl portions of which are optionally substituted by one or more R12; or R6 and R7 are joined so as together form a divalent radical having 4 to 6 atoms in the chain, this divalent radical being alkylene, alkyleneoxyalkylene or alkyleneaminoalkylene, preferably to form a morpholine, pyrrolidine, piperidine or piperazine ring;
R8 is alkyl or haloalkyl;
R9 is selected from alkyl, haloalkyl or the hydrogen atom;
R10 is selected from R9 or alkoxy;
R11 is alkyl or haloalkyl; or is selected from phenyl or heteroaryl that is optionally substituted by one or more groups selected from hydroxy, halogen, alkoxy, xe2x80x94S(O)rR8, cyano, R8 or combinations thereof;
R12 is selected from cyano, nitro, alkoxy, haloalkoxy, xe2x80x94S(O)s-alkyl, xe2x80x94S(O)s-haloalkyl, C(O)-alkyl, C(O)-haloalkyl, C(O)O-alkyl, C(O)O-haloalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, hydroxy, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl;
X is selected from the nitrogen atom, or the radical Cxe2x80x94R13;
R13 is a halogen atom; and
m, n, p, q, r and s represent, independently of one another, the values zero, one or two;
or a pesticidally acceptable salt thereof.
By the term xe2x80x9cpesticidally acceptable saltsxe2x80x9d is meant salts the anions and cations of which are known and accepted in the art for the formation of pesticidally acceptable salts. Preferably such salts are water soluble. Suitable acid addition salts formed from compounds of formula (I) containing an amine group, include salts with inorganic acids for example hydrochlorides, phosphates, sulfates and nitrates, and salts with organic acids for example acetates. Suitable salts formed with bases from compounds of formula (I) containing a carboxylic acid group, include alkali metal (for example sodium or potassium) salts, ammonium salts and organic amine (for example diethanolamine or morpholine) salts.
Unless otherwise specified alkyl and alkoxy groups have from one to four carbon atoms. The haloalkyl and haloalkoxy groups likewise preferably have one to four carbon atoms. The various individual aliphatic hydrocarbon moieties, that is, radicals and portions thereof (for example the alkyl moiety of alkylaminocarbonyl and alkylaminosulfonyl) have up to four carbon atoms in the chain.
The haloalkyl and haloalkoxy groups can bear one or more halogen atoms.
The term heteroaryl refers to a five to seven membered heterocyclic ring containing from one to four heteroatoms selected from nitrogen, oxygen and sulfur.
The term halogen means F, Cl, Br or I. The term xe2x80x9chaloxe2x80x9d before the name of a radical means that this radical is partially or completely halogenated, that is to say, substituted by F, Cl, Br or I, in any combination, preferably by F or Cl.
R2 is preferably an amino group, which is unsubstituted or which bears one or two substituents selected from the group consisting of alkyl, xe2x80x94C(O) R8 and xe2x80x94C(O)OR8; the alkyl portions of which are optionally substituted by one or more R12.
R3 is preferably a halogen atom; especially preferred is a chlorine atom; R4 is preferably selected from a halogen atom, haloalkyl, haloalkoxy, or xe2x80x94SF5; especially preferred are CF3xe2x80x94, CF3Oxe2x80x94 and xe2x80x94SF5.
R5 is preferably methyl, ethyl or propyl.
A particularly preferred group of compounds of general formula (I) because of their systemic aphicidal properties are those wherein:
R2 is NR6R7;
R3 is halogen;
R4 is CF3xe2x80x94, CF3Oxe2x80x94 or xe2x80x94SF5;
R5 is alkyl;
X is CR13;
R13 is halogen; and
m is 0 or 1.
A further particularly preferred class of compounds of general formula (I) because of their systemic aphicidal properties are those wherein:
R2 is NR6R7;
R3 is chlorine;
R4 is CF3xe2x80x94, CF3Oxe2x80x94 or xe2x80x94SF5;
R5 is alkyl;
R6 is hydrogen;
R7 is hydrogen, xe2x80x94S(O)qCF3, or alkyl optionally substituted by xe2x80x94S(O)sR8 or aminocarbonyl;
X is CR13;
R13 is chlorine or bromine; and
m is 0 or 1.
A further particularly preferred class of compounds of general formula (I) because of their systemic aphicidal properties are those wherein:
R2 is NR6R7;
R3 is chlorine;
R4 is CF3xe2x80x94 or xe2x80x94SF5;
R5 is methyl or ethyl;
R6 is hydrogen;
R7 is hydrogen, methyl or ethyl optionally substituted by xe2x80x94S(O)sR8 or aminocarbonyl;
R8 is methyl or ethyl;
R9 is methyl or ethyl;
X is CR13;
R13 is chlorine or bromine; and
m is 0 or 1.
Particularly preferred pyrazole derivatives usable in the method for control of insects within the scope of the present invention include the following. The numbers 1-12 are assigned to these compounds for reference and identification.
1. 3-acetyl-5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulfinylpyrazole
2. 3-acetyl-5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthiopyrazole
3. 3-acetyl-5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)4-ethylsulfinylpyrazole
4. 3-acetyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethylamino-4-methylsulfinylpyrazole
5. 3-acetyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylamino-4-methylsulfinylpyrazole
6. 3-acetyl-5-(carbamoylmethylamino)-1l-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulfinylpyrazole
7. 3-acetyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(2-ethylsulfonylethylamino)-4-methylsulfinylpyrazole
8. 3-acetyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(2-carbamoylmethylamino)-4-methylsulfinylpyrazole
9. 3-acetyl-5-amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-4-methylsulfinylpyrazole
10. 3-acetyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulfinyl-5-trifluoromethylsulfenylaminopyrazole
11. 3-acetyl-5-amino-1-(2,6-dichloro-4-pentafluorothiophenyl)-4-methylsulfinylpyrazole
12. 3-acetyl-5-amino-1-(2,6-dichloro-4-pentafluorothiophenyl)-4-methylthiopyrazole
Compounds 1 and 2 are preferred.
Among the compounds which can be used in the invention some are new and are a further feature of the instant invention. The following representative compounds of formula (I) also form part of the invention. In the Table below Et represents ethyl, Pr means n-propyl. Where subscripts are not shown they are intended, for example SCFCl2 means SCFCl2.
The compounds of formula (I) can be prepared according to the manufacturing processes described in International Patent Publications Nos. WO 94/21606 and WO 93/06089 or International Patent Publication No. WO 87/03781 as well as in European Patent Publication No. 0295117 and Hatton et al U.S. Pat. No. 5,232,940. Those skilled in the art will choose the proper initial reactant in these known methods and adapt these known methods to the said reactant so as to obtain the corresponding desired products. It is understood that in the description of the following processes the sequences for the introduction of the various groups on the pyrazole ring may be performed in a different order and that suitable protecting groups may be required as will be apparent to those skilled in the art.
In the following description of processes when symbols appearing in formulae are not specifically defined, it is to be understood that they are xe2x80x9cas defined abovexe2x80x9d in accordance with the first definition of each symbol in the specification.
According to a further feature of the present invention compounds of general formula (I) wherein R1, R2, R3, R4 and X are as defined above may be prepared by reacting compounds of formula (II): 
wherein R1, R2, R3, R4 and X are as defined above with an appropriate reagent CH3M wherein M is an alkali metal such as lithium; or an alkaline earth metal salt such as MgBr, MgCl, MgI in which case the CH3M is a Grignard reagent such as methyl magnesium bromide, methyl magnesium iodide and methyl magnesium chloride. The reaction can be conducted in a variety of solvents for example dichloromethane, dichloromethane, toluene, tetrahydrofuran and chlorobenzene which may be present as a mixture, at a temperature ranging from xe2x88x9270xc2x0 C. to 120xc2x0 C., preferably from xe2x88x9220xc2x0 C. to 50xc2x0 C. The reaction may be catalyzed by acids including Lewis acid, such as but not limited to AlCl3, BBr3, TiCl4, BF3, SiCl4, BCl3, CuBr.
According to a further feature of the invention compounds of general formula (I) wherein R1, R2, R3, R4 and X are as defined above and m represents 0 or 1 may be prepared directly by reacting the corresponding compounds of formula 
with an appropriate reagent R5S(O)mY wherein m represents 0 or 1 and Y is halogen (preferably chlorine). The transformation of the compounds of formula (III) into compounds of formula(I) can be achieved by the direct sulfenylation or sulfinylation using the appropriate alkylsulfenyl halides or alkylsulfinyl halides, such as methylsulfenyl halide or methylsulfinyl halide. The alkylsulfenyl halides and alkylsulfinyl halides can be prepared in a separate pot or optionally in situ in the medium used for reaction with the compounds of formula (III). Inert solvents are generally used for example methyl t-butyl ether, dichloroethane; toluene and chlorobenzene. The reaction can be conducted in the presence of catalyst which may be basic, for example a metal carbonate, a metal hydride such as a sodium hydride, or a metal hydroxide such as a sodium hydroxide. The reaction can be carried out at a temperature from about xe2x88x9220xc2x0 C. to about 120xc2x0 C., preferably at a temperature of from 0xc2x0 C. to 100xc2x0 C.
According to a further feature of the invention compounds of general formula (I) wherein R1, R3, R4 and X are as defined above and R2 represents amino may be prepared by the reaction of a compound of formula (IV): 
with a compound of formula (V): 
The reaction is performed in the presence of a base for example a metal alkoxide preferably sodium ethoxide in an inert solvent for example ethanol at a temperature from 0xc2x0 C. to the reflux temperature.
According to a further feature of the invention compounds of general formula (I) wherein R1, R2, R3, R4 and X are as defined above and wherein m represents 1 or 2 may be prepared by the oxidation of the corresponding compounds of formula (I) in which m represents 0 or 1. The reaction is preferably performed with a peracid such as 3. -chloroperbenzoic acid in an inert solvent for example methylene chloride at a temperature from 0xc2x0 C. to the reflux temperature of the solvent.
According to a further feature of the present invention compounds of general formula (I) wherein R2 represents NR6R7, xe2x80x94S(O)nR8, C(O)OH, alkyl, haloalkyl, or
xe2x80x94Nxe2x95x90C(R10)(R11) wherein R6 and/or R7 represent alkyl, haloalkyl, xe2x80x94C(O) R8, C(O)OR8, and xe2x80x94S(O)qCF3; the alkyl portions of which are optionally substituted by one or more R12; or R6 and R7 are joined so as together form a divalent radical having 4 to 6 atoms in the chain, may be prepared from the corresponding compounds in which R2 is amino by methods described in one or more of International Publications No. WO 94/21606, WO 93/06089 and WO 87/03781, European Patent Publication No. 0295117 and EP 511845, Hatton et al U.S. Pat. No. 5,232,940, German Patent Publication No. DE 19511269, and EP 780378.
According to a further feature of the invention compounds of general formula (I) wherein R1, R3, R4 and X are as defined above and R2 represents NR6R7 wherein R6 represents hydrogen and R7 represents ethyl substituted at the 2-position by R12 wherein R12 represents cyano, nitro, xe2x80x94S(O)sR8, C(O)R8, C(O)OR9, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl, may be prepared by the reaction of the corresponding compound of formula (I) wherein R2 is amino with a compound of formula (VI):
R12xe2x80x94CHxe2x95x90CH2xe2x80x83xe2x80x83(VI)
wherein R12 is defined above. The reaction may be performed optionally in the presence of a base such as sodium hydride, an alkali metal hydroxide for example potassium hydroxide, or a tetraalkylammonium hydroxide for example N-benzyltrimethylammonium hydroxide in a solvent such as toluene, ethanol or water, and at a temperature from xe2x88x9220xc2x0 C. to the reflux temperature.
According to a further feature of the invention compounds of general formula (I) wherein R1, R3, R4 and X are-as defined above and R2 represents NR6R7 wherein R6 and/or R7 represent alkyl or haloalkyl optionally substituted by one or more R12, may be prepared by the reaction of the corresponding compound of formula (I) wherein R2 is amino with a compound of formula (VII):
R14xe2x80x94Yxe2x80x83xe2x80x83(VII)
wherein R14 is alkyl or haloalkyl optionally substituted by one or more R12 and Y represents a leaving group preferably halogen for example chlorine. The reaction is performed in the presence of a base such as potassium hydroxide, potassium methoxide, sodium hydride or triethylamine in an inert solvent such as methyl t-butyl ether or toluene, and at a temperature from xe2x88x9220xc2x0 C. to the reflux temperature.
According to a further feature of the present invention compounds of general formula (I) wherein R2 represents C(O)OR8 may be prepared by the reaction of the corresponding compound of formula (I) in which R2 is carboxy with an alcohol of formula (VIII):
R8OHxe2x80x83xe2x80x83(VIII)
The above reaction is generally performed in the presence of an acid catalyst such as sulphuric acid generally in the presence of excess of the alcohol or optionally in a co-solvent at a temperature from 0xc2x0 C. to the reflux temperature. Alternatively the reaction may be performed using a coupling reagent such as dicyclohexylcarbodiimide (DCC) in an inert solvent.
According to a further feature of the present invention compounds of general formula (I) wherein R2 represents carboxy may be prepared by the oxidation of the corresponding compound of formula (I) in which R2 is replaced by formyl. The reaction is generally carried out using potassium permanganate or chromic acid in a solvent such as water at 0xc2x0 C. to the reflux temperature.
According to a further feature of the present invention compounds of general formula (I) wherein R2 represents RaCH(Cl)CH2xe2x80x94 wherein Ra represents alkyl may be prepared by the diazotisation of the corresponding compound of formula (I) in which R2 represents amino and reaction with a compound of formula (IX):
RaCHxe2x95x90CH2xe2x80x83xe2x80x83(IX)
The reaction is generally carried out using an alkyl nitrite such as tert-butyl nitrite in the presence of a copper salt such as copper (II) chloride in a solvent such as acetonitrile at a temperature from xe2x88x9210xc2x0 C. to 50xc2x0 C.
According to a further feature of the present invention compounds of general formula (I) wherein R2 represents C(O)R8 may be prepared by the oxidation of the corresponding compound of formula (X): 
wherein R1, R3, R4, R8 and X are as defined above. The reaction may be performed using for example a mixture of chromic acid and sulphuric acid in a solvent such as water and acetone at a temperature from 0xc2x0 C. to 60xc2x0 C.
According to a further feature of the present invention compounds of general formula (I) wherein R2 represents OR9 may be prepared by methods described in U.S. Pat. Nos. 5,047,550 and 4,918,085.
Intermediates of formula (II) wherein R1 represents S(O)mR5 and wherein m represents 1 or 2 may be prepared by the reaction of a compound of formula (XI): 
with a reagent of formula R5S(O)mY wherein Y represents halogen preferably chlorine using the above described method for the preparation of compounds of formula (I) from compounds of formula III).
Intermediates of formula (III) wherein R2 is amino can be prepared by diazotisation of a compound of formula (XII): 
and reaction of the resultant diazonium salt of formula with a reagent of formula (XIII): 
The diazotisation of compounds of formula (II) may be performed by well documented procedures. The reaction of the diazonium salts with compounds of formula (XIII) to give compounds of formula (III) wherein R2 is amino can be achieved via a two step process involving coupling and subsequent ring closure which may be performed in the same vessel. The condensation can be achieved in the presence of appropriate acids such as acetic acid or hydrochloric acid or in the presence of a basic catalyst such as sodium acetate. The reaction can be carried out in a variety of solvents including alcohols such as ethanol or ethers such as methyl t-butyl ether, optionally in admixture with water, generally at a temperature from about xe2x88x9230xc2x0 C. to 100xc2x0 C. preferably from 0xc2x0 C. to 50xc2x0 C. The ring closure step is preferably carried out in the presence of base catalyst in appropriate solvents including but not limited to those employed in the first (coupling) stage of the reaction. The base catalyst used can be an organic base for example triethylamine or pyridine; amidines such as 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) or an inorganic base such as ammonia, sodium bicarbonate or sodium hydroxide. The reaction can be conducted from about xe2x88x9230xc2x0 C. to about 120xc2x0 C., preferably from 0xc2x0 C. to 100xc2x0 C.
Intermediates of formula (X) can be prepared by reaction of the corresponding compounds of formula (I) in which R2 is replaced by a formyl group with an organometallic reagent of formula R8 Q wherein Q is preferably an alkali or alkaline earth metal for example a magnesium halide (Grignard) reagent. The reaction may be performed in an inert solvent such as methyl t-butyl ether at a temperature from xe2x88x9278xc2x0 C. to the reflux temperature of the solvent.
Intermediates of formula (I) in which R2 is replaced by a formyl group may be prepared by the oxidation of the corresponding compound of formula (I) in which R2 represents RaCHxe2x95x90CHxe2x80x94. The reaction is generally performed using a reagent such as ozone or sodium metaperiodite in an inert solvent for example dichloroethane at a temperature from xe2x88x92100xc2x0 C. to 100xc2x0 C.
Intermediates of formula (I) in which R2 is replaced by RaCHxe2x95x90CHxe2x80x94 may be prepared by the dehydrochlorination of the corresponding compound of formula (I) in which R2 represents RaCH(Cl)CH2xe2x80x94. The reaction is generally performed using a base such as sodium hydroxide or triethylamine in an inert solvent for example dichloroethane at a temperature from xe2x88x9270xc2x0 C. to the reflux temperature.
Synthesis of intermediate compounds of general formula (XII) can be achieved according to variations of known methods, for example, those described in WO 93/06089, as well as in Hatton et al U.S. Pat. No. 5,232,940.
Certain compounds of formula (II) are novel and as such form a further feature of the present invention.
Intermediates of formula (IV) and (V) are known or may be prepared by known methods.